Micro-rnas and compositions comprising same for the treatment and diagnosis of serotonin-, adrenalin-, noradrenalin-, glutamate-, and corticotropin-releasing hormone- associated medical conditions

Abstract

microRNAs and compositions comprising same for the treatment and diagnosis of serotonin-, adrenalin-, noradrenalin-, glutamate-, and corticotropin-releasing hormone-associated medical conditions are provided.

What is claimed is: 
     
         1 . A method of treating a medical condition in which a low glutamate receptor level is therapeutically beneficial in a subject in need thereof, the method comprising administering to said subject miR-181 or a precursor thereof or expressing in a cell of said subject an exogenous polynucleotide encoding a miR-181 or a precursor thereof, thereby treating the medical condition. 
     
     
         2 . The method of  claim 1 , wherein said medical condition is selected from the group consisting of a seizure, a Huntington's disease, a schizophrenia, a fragile X syndrome, a generalized anxiety disorder, a memory impairment and a cancer. 
     
     
         3 . The method of  claim 1 , wherein said subject is a human subject. 
     
     
         4 . The method of  claim 1 , wherein said miR-181 is as set forth in SEQ ID NO: 85-94. 
     
     
         5 . The method of  claim 1 , wherein said miR-181 comprises a modification selected from the group consisting of a modified backbone, a modified internucleoside linkage and a modified base. 
     
     
         6 . The method of  claim 5 , wherein said modification is selected from the group consisting of a phosphorothioate, a chiral phosphorothioate, a phosphorodithioate, a phosphotriester, an aminoalkyl phosphotriester, a methyl phosphonate, an alkyl phosphonate, a chiral phosphonate, a phosphinate, a phosphoramidate, an aminoalkylphosphoramidate, a thionophosphoramidate, a thionoalkylphosphonate, a thionoalkylphosphotriester, a boranophosphate, a peptide nucleic acid (PNA), a 2′-O-methoxyethyl, a 2′-O-methyl and a 2′-fluoro. 
     
     
         7 . The method of  claim 1 , wherein said miR-181 comprises a modification in both a sugar and an internucleoside linkage. 
     
     
         8 . The method of  claim 1 , wherein said cell is a neuroglia cell. 
     
     
         9 . An isolated cell comprising a nucleic acid construct expressing a miR-181 or a precursor thereof under a transcriptional control of a cis acting regulatory element. 
     
     
         10 . The isolated cell of  claim 9 , wherein said cell is a neuroglia cell. 
     
     
         11 . The isolated cell of  claim 9 , wherein said miR-181 is as set forth in SEQ ID NO: 85-94. 
     
     
         12 . A nucleic acid construct comprising a nucleic acid sequence encoding a miR-181 or a precursor thereof, said nucleic acid sequence being under a transcriptional control of a cis acting regulatory element. 
     
     
         13 . The nucleic acid construct of  claim 12 , wherein said cis acting regulatory element is active in a neuroglia cell or a cardiac cell. 
     
     
         14 . A pharmaceutical composition comprising the nucleic acid construct of  claim 12  and a pharmaceutically acceptable carrier or diluent. 
     
     
         15 . A method of regulating an expression of a glutamate receptor gene in a neuroglia cell, the method comprising modulating an activity or expression of miR-181 or a precursor thereof in said neuroglia cell, thereby regulating the expression of the glutamate receptor gene. 
     
     
         16 . The method of  claim 15 , wherein said glutamate receptor gene is selected from the group consisting of glutamate receptor metabotropic 1 (Grm1), glutamate receptor ionotropic kainate 3 (Grik3), glutamate receptor metabotropic 5 (Grm5), glutamate receptor ionotropic kainate 2 (Grik2) and glutamate receptor metabotropic 7 (Grm7).